A human tissue map of 5-hydroxymethylcytosines exhibits tissue specificity through gene and enhancer modulation

  • Nat Commun. 2020 Dec 2;11(1):6161. doi: 10.1038/s41467-020-20001-w.
Xiao-Long Cui  1  2 ,  Ji Nie  1  2 ,  Jeremy Ku  3 ,  Urszula Dougherty  4 ,  Diana C West-Szymanski  2  4 ,  Francois Collin  3 ,  Christopher K Ellison  3 ,  Laura Sieh  1  2 ,  Yuhong Ning  3 ,  Zifeng Deng  4 ,  Carolyn W T Zhao  1  2 ,  Anna Bergamaschi  3 ,  Joel Pekow  4 ,  Jiangbo Wei  1  2 ,  Alana V Beadell  1  2 ,  Zhou Zhang  5 ,  Geeta Sharma  6 ,  Raman Talwar  3 ,  Patrick Arensdorf  3 ,  Jason Karpus  1  2 ,  Ajay Goel  6 ,  Marc Bissonnette  4 ,  Wei Zhang  5 ,  Samuel Levy  3 ,  Chuan He  7  8
Affiliations
  • 1. Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, USA.
  • 2. Howard Hughes Medical Institute, University of Chicago, Chicago, IL, USA.
  • 3. Bluestar Genomics Inc., San Diego, CA, USA.
  • 4. Department of Medicine, University of Chicago, Chicago, IL, USA.
  • 5. Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • 6. City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
  • 7. Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, USA. [email protected].
  • 8. Howard Hughes Medical Institute, University of Chicago, Chicago, IL, USA. [email protected].
PMID: 33268789 DOI: 10.1038/s41467-020-20001-w
Abstract

DNA 5-hydroxymethylcytosine (5hmC) modification is known to be associated with gene transcription and frequently used as a MARK to investigate dynamic DNA methylation conversion during mammalian development and in human diseases. However, the lack of genome-wide 5hmC profiles in different human tissue types impedes drawing generalized conclusions about how 5hmC is implicated in transcription activity and tissue specificity. To meet this need, we describe the development of a 5hmC tissue map by characterizing the genomic distributions of 5hmC in 19 human tissues derived from ten organ systems. Subsequent Sequencing results enabled the identification of genome-wide 5hmC distributions that uniquely separates samples by tissue type. Further comparison of the 5hmC profiles with transcriptomes and histone modifications revealed that 5hmC is preferentially enriched on tissue-specific gene bodies and enhancers. Taken together, the results provide an extensive 5hmC map across diverse human tissue types that suggests a potential role of 5hmC in tissue-specific development; as well as a resource to facilitate future studies of DNA demethylation in pathogenesis and the development of 5hmC as biomarkers.

Products